Method of preparing glycocyamidines



Patented June 19, 1951 UNITED STATES PATENT OFFICE METHOD OF PREPARINGGLYCO- CYAMIDIN ES Erick I. Hoegberg, Stamford, Conn., assignor toAmerican Cyanamid Company, New York, N. Y., a corporation of Maine NoDrawing. Application April 19, 1950, Serial No. 156,933

I eral formula HN=O2 4 \i/ in which R represents a member of the groupconsisting of alkyl and aryl radicals, and R represents a member of thegroup consisting, of hydrogen, alkyl and aryl radicals, such as, forexample, l-n-butylglycocyamidine, l-n-octylglycocyamidine,l-dodecylglycocyamidine, l-octadecylglycocyamidine,l-phenylglycocyamidine, 1, 3- diphenylglycocyamidine, l-phenyl 3ethylglycocyamidine, l-phenyl-3-allyglycocyamidine, 1-phenyl-3-cyclohexylglycocyamidine, 1-phenyl-3- n-octylglycocyamidine,l-phenyls3-decylglycocyamidine, l-n-amyl-3-isopropylglycocyamidine, 1-n-octyl-3-n-buty1g1ycocyamidine, l-n-octyl 3 tetradecylglycocyamidine, 1-n-butyl-3 -(1-naphthyD-glycocyamidine, and l (2 ethylheXy1)-3-phenylglycocyamidine.

It has been discovered that a glycocyamidine of the above type maybereadily prepared by reacting an alkali-forming metal salt of. amonosubstituted cyanamide of the formula.

in which M is an alkali-forming metal, 2 is an integer not greater than2 and R. has the meaning shown above, with a haloacetamide of theformula X-CHi in which X is a halogen and R has the meaning shown above,in the presence of a solvent.

The term alkali-forming metal as used in this specification and claimsis intended to cover the alkali and alkaline earth metals.

A typical reaction in which sodium phenylcyanamide is reacted witha-blOIl'lO-N-Il-OCtYlacetamide to produce 1-phenyl-3 noctylglycocyamidine may be illustrated as follows:

Typical examples of solvents which may be employed in the presses arewater, the low molecular Weight aliphatic monohyclric alcohols such as,for example, methyl, ethyl, isopropy1,n-propyl, n-butyl, tert.-buty1 andsec.-amyl alcohol; ketones such as acetone, methy ethyl ketone, methyln-propyl ketone, methyl isobutyl ketone, methyl benzyl ketone,cyclohexanone, and acetophenone; alkyl esters ofaliphaticmonocarboxylic' acids having boiling points less than 200 C. such asethyl acetate, n-propyl acetate, n-butyl acetate, iso-butyl acetate,2-ethylhexyl acetate, ethyl propionate, methyl butyrate and n-propylvalerate; aromatic nitriles and aliphatic saturated nitriles havingboiling points not greater than 220 C. such as benzonitrile,acetonitrile, propionitrile, isobutyronitrile, and n-capronitrile.

The reaction is preferably carried out at a temperature within the rangeof from about 20 to 0.. However, temperatures outside of this range maybe employed depending upon the type of reactants and solvents utilized.

The invention is further illustrated by the following examples in-whichthe parts areby weight.

Example 1 hours.

Example 2 A mixture of 14 parts of sodium phenylcyanamide, 9.4 parts ofchloroacetamide and 200 parts of acetone was heated to reflux for aperiod of 4 hours in a vessel equipped with a stirrer and refiuxcondenser. The mixture was cooled to room temperature and filtered. Thefilter cake was washed with water and then dried at 65 0., giving 9.1parts of l-phenylglycocyamidine.

Example 3 Example 2 was repeated using 200 parts of acetonitrile inplace of the acetone as the solvent for the reactants. 10.6 parts ofl-phenylglycocyamidine were obtained.

Example 4 Example 2 was repeated using 200 parts of ethyl acetate inplace of the acetone. 12.5 parts (71% yield) of l-phenylglycocyamidinewere obtained.

Example 5 A mixture of 4.4 parts of sodium n-octylcyanamide, 2.4 partsof chloroacetamide and 100 parts of acetone was heated to reflux forthree The acetone was distilled on and the residue was washed with waterto remove the by-product sodium chloride. 3.12 parts ofl-noctylglycocyamidine were obtained. After recrystallization fromalcohol, the product was a colorless crystalline material melting at239"- 244" C.

Example 6 A mixture of 14 parts of sodium phenylcyanamide, 25 parts ofa-bromo-N-n-octylacetamide and 100 parts of ethyl alcohol was heated toreflux for two hours and then allowed to stand at room temperature for16 hours. The reaction mixture was filtered to remove the precipitatedsodium bromide. The filtrate was heated to distill off the ethylalcohol. The residue was recrystallized twice from methyl alcohol,giving 8 parts of 1-phenyl-3-n-octylglycocyamidine, a colorlesscrystalline material melting at 3688 C.

Example 7 A mixture of 14 parts of sodium phenylcyanamide, 17 parts ofa-chloroacetanilide and 300 parts of acetone was warmed on a steam bathfor one hour, then allowed to stand at room temperature for 48 hours.The acetone was distilled off, and the residue was washed with water anddried at 65 C. 22 parts (87% yield) of 1,3-diphenylglycocyamidine wereobtained. After recrystallization from acetone, the product was acolorless crystalline material melting at 164-l65 C.

Example 8 A mixture of 14 parts of sodium phenylcyanamide, 21.5 parts ofa-chloro-p-nitroacetanilide and 150 parts of ethyl alcohol was heated toreflux for three hours and then allowed to stand at room temperature for16 hours. The reaction mixture was filtered. The filter cake was washedwith water and then dried, giving 23 parts (78% yield) of1-pheny1-3-p-nitropheny1glycocyamidine. After recrystallization fromacetone, the product was a yellow, crystallin material melting at271-273 C.

Example 9 8.73 parts of sodium-p-chlorophenylcyanamide and 4.68 parts ofchloroacetamide were dissolved in parts of water and allowed to stand atroom temperature for 48 hours. The resulting precipitate was filtered,washed with water and dried at C. 7 parts (67% yield) ofl-p-chlorophenylglycocyamidine were obtained. After recrystallizationfrom acetone, the product was a tan-colored, crystalline materialmelting at 275-278 C. with decomposition.

The glycocyamidines, prepared by the methods of the present invention,are adapted for various uses, more particularly as chemotherapeuticagents, bactericides, and catalysts for the polymerization ofunsaturated organic compounds to form high molecular weight linearpolymers.

While the invention has been described with particular reference tospecific embodiments, it is to be understood that it is not to belimited thereto but is to be construed broadly and restricted solely bythe scope of the appended claims.

I claim:

1. A method of preparing a glycocyamidine of the general formula whereinR represents a member of the group consisting of alkyl and arylradicals, and R represents a member of the group consisting of hydrogen,alkyl and aryl radicals, which comprises reacting an alkali-formingmetal salt of a monosubstituted cyanamide of the formula RN M a in whichM is an alkali-forming metal, a is an integer not greater than 2 and Ris a member of the group consisting of alkyl and aryl radicals, with ahaloacetamide of the formula X-CH C=O r sen in which X is a halogen andR is a member of the group consisting of hydrogen, alkyl and arylradicals, in the presence of a solvent, and recovering theglycocyamidine.

2. The method of claim 1 in which the reaction is .carried out at atemperature within the range of from about 20-150 C.

3. A method of preparing l-phenylglycocyami- .dine which comprisesreacting sodium phenylcyanamide withv chloroacetamide in the presence ofa solvent, and recovering the 1-phenylglycocyamidine.

4. A method of preparing l-n-octylglycocyamidine which comprisesreacting sodium n-octylcyanamide with chloroacetamide in the presence ofa solvent, and recovering the l-n-octylglycocyamidine.

5. A method of preparing 1-phenyl-3-n-octylglycocyamidine whichcomprises reacting sodium phenylcyanamide witha-bromo-N-n-octylacetamide in the presence of a solvent, and recoveringthe 1-phenyl-3n-octylglycocyamidine.

ERICK I. HOEGBERG.

No references cited.

7 Patent No. 2,557 ,911

Certificate of Correction June 19, 1951 ERICK I. HOEGBERG It is herebycertified that error appears in the printed specification of the abovenumbered patent requiring correction as follows:

Column 2, line 17, for presses read process;

and that the said Letters Patent should be read as corrected above, sothat the same may conform to the record of the case in the PatentOflice.

Signed and sealed this 28th day of August, A. D. 1951.

THOMAS F. MURPHY,

Assistant (Jommiasz'oner of Patents.

1. A METHOD OF PREPARING A GLYCOCYAMIDINE OF THE GENERAL FORMULA